Differential Diagnosis of acute polyarthritis

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Transcript Differential Diagnosis of acute polyarthritis

How do polyarthritis, polyarthralgias, and diffuse aches
and pains differ
 Polyarthritis is definite inflammation (swelling, tenderness,
warmth) of more than four joints demonstrated by physical
examination. A patient with two to four involved joints is said to
have pauci- or oligoarticular arthritis.
 Polyarthralgia is defined as pain in more than four joints without
demonstrable inflammation by physical examination. The
chronic noninflammatory arthritides commonly present with
 Diffuse aches and pains are poorly localized symptoms
originating in joints, bones, muscles, or other soft tissues. A joint
examination does not reveal inflammation. Polymyalgia
rheumatica, fibromyalgia, SLE, polymyositis, and
hypothyroidism commonly present with these symptoms.
Time Course of Joint Symptoms
 Polyarticular joint symptoms may have an acute or
insidious onset.
 Acute polyarthritis, especially when accompanied by fever,
is always due to an inflammatory disease and requires
immediate evaluation to rule out infection or crystalline
arthritis .
 Alternatively, there are both inflammatory and noninflammatory causes of polyarthritis with an insidious
 Variations, however, may occur, and a disorder that
typically has an insidious onset may have an acute onset in
some patients.
Pattern of Joint Involvement
 The additive pattern is most common but least specific. It
refers to recruitment of new joints while previously
involved joints remain involved and is commonly seen in
RA and other systemic rheumatic diseases.
 A migratory pattern refers to symptoms being present in
certain joints for a few days and then remit, only to
reappear in other joints. This pattern is most characteristic
of rheumatic fever, the early phases of Neisserial infection
and Lyme disease, and acute childhood leukemia
 An intermittent pattern is typified by repetitive attacks of acute
polyarthritis with complete remission between attacks.
Palindromic rheumatism, crystal-induced diseases, familial
Mediterranean fever, and Whipple’s disease can intermittently
affect joints for a few to several days at a time, followed by
asymptomatic periods of varying length over a number of years.
 RA, relapsing seronegative symmetrical synovitis with pitting
edema (RS3PE syndrome), systemic lupus erythematosus (SLE),
sarcoidosis, and Still’s disease can also appear episodically,
particularly early in their disease course.
 The seronegative spondyloarthropathies may have an
intermittent course, but the articular symptoms in these diseases
last for weeks (not days) at a time before resolving.
Pain Characteristics
 Inflammatory joint pain involves the joints diffusely and is
present at rest and with normal use. Nocturnal pain may
interfere with sleep.
 This joint pain is associated with prolonged stiffness for
greater than 30 to 60 minutes, which is worse in the
morning or after inactivity (gelling).
 Fatigue is common, may be severe, and typically occurs by
early afternoon after stiffness has improved.
 Patients with non-inflammatory joint pain have pain with
activity that is relieved by rest. Although they may have
stiffness or gelling after inactivity, it typically lasts less than
15 minutes, and systemic fatigue is not common.
Number and Distribution of Joint Involvement
 Polyarthritis refers to involvement of five or more joints.
The joint distribution typically is symmetric, although
distribution may go through an initial asymmetric phase.
 The most common identifiable cause of a self-limited
disorder causing acute symmetric polyarthritis involving
the small joints of the hands and wrists is parvovirusassociated arthritis.
 The most common cause of a chronic inflammatory
polyarthritis that involves small and large joints bilaterally
and symmetrically in the upper and lower extremities is
 The metacarpopha-langeal (MCP) joints and proximal
interphalangeal (PIP) joints of the fingers,
metatarsophalangeal (MTP) joints of the feet, and wrists
are commonly affected, while the distal interphalangeal
(DIP) joints, lumbar spine, and sacroiliac joints are spared.
 Inflammatory arthritis in an RA pattern but also involving
the DIP joints of the fingers should always suggest psoriatic
arthritis or multicentric reticulohistiocytosis.
 Any patient with inflammatory arthritis involving both
ankles predominantly should be evaluated for acute sarcoid
 A number of non-inflammatory disorders may cause a
chronic polyarthritis.
 The most common of these is primary generalized
osteoarthritis, which typically involves the DIPs, PIPs,
and first carpometacarpal (CMC) joint of the fingers,
hips, knees, and first MTP.
 Hemochromatosis and calcium pyrophosphate disease
(CPPD) should be considered in a patient with chronic
non-inflammatory polyarthritis involving the MCPs,
wrists, shoulders, and ankles, which are joints not
typically involved with osteoarthritis.
Associated Extra-Articular Symptoms and Medical Conditions
 The presence of past or current extra-articular manifestations may
provide important clues to the etiology of polyarticular arthritis .
 Fever suggests a subset of illness including infection (viral, bacterial),
postinfectious (rheumatic fever, reactive arthritis), systemic rheumatic
diseases (RA, SLE, Still’s disease, vasculitis, IBD), crystal-induced
diseases (gout, pseudo-gout), and miscellaneous diseases (malignancy,
sarcoidosis ) . Night sweats and weight loss may also be important.
 Rashes such as psoriatic plaques, erythema migrans (Lyme disease),
erythema nodosum (IBD, sarcoidosis), erythema marginatum
(rheumatic fever), and butterfly malar rash (SLE), among others, can
be particularly useful in the diagnosis.
 Other potentially important diagnostic clues are a history of Raynaud’s
disease, serositis, oral ulcers (IBD, Behçet’s disease), or involvement of
the lungs, heart, kidney, or liver .
 Other important associated symptoms include a history of
diarrhea, abdominal pain, urethral discharge, low back pain, and
uveitis, which may indicate a reactive arthritis or other
 A review of a patient’s concomitant medical conditions,
medications, travel, and social history is important.
 Certain disorders, like renal insufficiency, obesity, and
alcoholism, or use of medications such as diuretics and
cyclosporine, among others, are associated with gouty arthritis,
while hyperparathyroidism and hemochromatosis are associated
with chondrocalcinosis and pseudogout.
 The sexual history should be elicited to help exclude reactive
arthritis, gonococcal arthritis, and human immunodeficiency
virus (HIV) exposures.
 A history of blood transfusions or intravenous drug
use puts patients at risk for hepatitis B, hepatitis C,
HIV, or septic arthritis.
 The use of certain medications, such as procainamide,
hydralazine, and minocycline, can cause drug-induced
 Frequent exposure to children may predispose to parvovirus infection and rheumatic fever.
 Tobacco abuse may indicate lung cancer in a patient
with hypertrophic osteoarthropathy.
Physical Examination
 The physical examination should be used to verify the
presence of historical features as well as additional findings
the patient may have not reported.
 Vital signs can help determine the severity of the illness
with fever being most important.
 Other findings on general examination that suggest a
systemic disorder include:
 lymphadenopathy, parotid enlargement, oral and genital
ulcers, eye disease (conjunctivitis, uveitis, scleritis, keratoconjunctivitis sicca, funduscopic abnormalities),
 heart murmurs (subacute bacterial endocarditis,
rheumatic fever), bruits, pericardial or pleural friction rubs.
Physical Examination
 fine inspiratory rales due to interstitial lung disease,
 hepatosplenomegaly,
 muscle weakness (polymyositis), and any neurologic
abnormalities (vasculitis)
 Particular attention should be given to the skin and
nails, looking for characteristic rashes or nodules
(rheumatoid, tophi, or, rarely, xanthomas or amyloid
Physical Examination
 In addition to symptomatic joints, all 66 joint areas should be
Particular attention should be given to the spine examination to
rule out an underlying axial arthritis.
Upon examination of the symptomatic joints, the presence or
absence of synovitis should be documented.
The detection of synovitis limits the differential diagnosis to an
inflammatory arthritis and is characterized by diffuse
involvement of the joint with tenderness, soft tissue swelling,
warmth over the joint, and possibly a joint effusion. Active and
passive range of motion will be limited in all planes.
Significant erythema should suggest an infectious or crystalline
Physical Examination
 Crepitus may be heard or felt as the joint is put through a
range of motion. Fine crepitus can arise from synovitis,
while more medium crepitus can arise from grating of
roughened cartilage surfaces or from bone rubbing against
 The examination of symptomatic joints in patients with a
non-inflammatory arthritis typically shows diffuse
involvement with tenderness, bony enlargement or spurs,
minimal if any warmth, and no erythema. An effusion,
particularly in the knee, may be demonstrated. Range of
motion is limited, both passively and actively, in all planes,
and medium or coarse crepitus may be felt.
Laboratory Studies
 A complete blood count, biochemical tests of renal and liver
function, and a urinalysis may help to identify patients with a
systemic illness.
 Serum uric acid levels are usually elevated in gout but can be
normal, particularly in patients with a polyarticular onset.
 An elevated erythrocyte sedimentation rate (ESR) and Creactive protein (CRP) are not specific but are elevated in over
90% of patients with an inflammatory cause for their
 Unfortunately, patients with non-inflammatory arthritides may
have an elevated ESR/CRP because of another problem such as
diabetes, dysproteinemia, or occult malignancy.
Laboratory Studies
 Specific antibody tests can identify exposure to potential
pathogens such as Group A streptococcus (antistreptolysin O
antibody), parvovirus B19, hepatitis B and C, Epstein–Barr virus,
and Borrelia burgdorferi(Lyme disease) and should be ordered
when these diseases are suspected clinically.
 Rheumatoid factor should be ordered in patients suspected to
have RA but can also be present in high titers in patients with
other diseases which can cause a polyarthritis resembling RA,
such as SLE, subacute bacterial endocarditis, and hepatitis C.
 The ANA test has high sensitivity but low specificity for SLE. A
negative ANA rules out SLE whereas a positive ANA with specific
antibodies to double-stranded DNA or Smith (Sm) are virtually
diagnostic of SLE in a patient with polyarthritis.
Laboratory Studies
 Synovial fluid should be obtained for total white blood
cell count, crystal examination, and cultures when the
diagnosis remains uncertain after history, physical
examination, and standard laboratory tests.
 Synovial fluid is only diagnostic in patients with
infections, gout, and pseudogout.
 Otherwise, synovial fluid analysis can only classify the
polyarthritis as inflammatory (>2000 WBC/mm3) or
non-inflammatory based on the synovial fluid WBC
Radiographic Studies
 In an appropriate clinical setting, plain radiographs may be
supportive of a particular diagnosis.
The findings of chondrocalcinosis and osteoarthritic changes
suggest, but do not prove, these diagnoses without
corresponding synovial fluid analysis.
In acute polyarthritis, radiographs lack specificity and usually
only show soft tissue swelling and intra-articular fluid.
In chronic inflammatory polyarthritis, marginal joint erosions
are seen earliest in the small joints of the hands, wrists, and feet
in patients with RA.
Chronic gout can also cause erosions with an overhanging edge
that typically involve small peripheral joints such as the first
MTP joint.
Differential diagnosis of acute polyarthritis
Differential Diagnosis of acute
 Many acute viral infections cause joint symptoms, with
polyarthralgias being considerably more common than true polyarthritis. The prevalence of polyarthritis is high, however, in adults
with acute erythrovirus (parvovirus B19) infection.
 The pattern of viral polyarthritis often mimics that of rheumatoid
arthritis. Adults with acute erythrovirus (parvovirus B19) infection,
the cause of “slapped cheek fever” in children, usually have only a
faint rash on the trunk or no rash at all.
 IgM antibodies to erythrovirus (parvovirus B19) are generally
present at the onset of joint symptoms and persist for
approximately 2 months.
 Acute hepatitis B causes an immune complex–mediated arthritis,
often with urticaria or maculopapular rash, during the preicteric
phase of infection; tests for hepatitis B surface antigen are positive.
Differential Diagnosis of acute polyarthritis
 Adult and juvenile rheumatoid arthritis and psoriatic
arthritis can present as acute polyarthritis but typically
have a more insidious onset.
 Both children and adults can develop Still’s disease,
which is characterized by high spiking fevers, polyarthritis,
pericarditis, an evanescent truncal rash, neutrophilic
leukocytosis, and the absence of a rheumatoid factor and
ANA. The fever characteristically spikes up to 104°F once or
twice a day and returns to normal or below normal
between fever spikes. The synovitis may be intermittent
initially, but a persistent polyarthritis develops in most
Differential Diagnosis of acute
 Systemic lupus erythematosusmay present with acute
polyarthritis that can be additive, migratory, or intermittent and may occur with fever. Characteristic
rashes, other extra-articular manifestations, and a
positive ANA support the diagnosis.
Differential diagnosis of chronic polyarthritis
Rheumatoid Arthritis
 Rheumatoid arthrtisis is the most common cause of a chronic
inflammatory polyarthritis. Approximately 30% to 40% of patients
presenting to an early polyarthritis clinic have RA .
Patients classically present with a symmetric polyarthritis that usually
affects MCPs, PIPs, wrists, and MTPs.
Prolonged morning stiffness upon awakening and gelling after periods
of inactivity are common.
Proliferative synovitis of symptomatic joints may lead to deformities
and erosions on radiographs.
Extra-articular manifestations include subcutaneous nodules (25%),
pleural effusions, episcleritis, and vasculitis, among others.
Rheumatoid factor is positive in 70% to 85% of patients, while antiCCP is positive in only 50% to 60% of patients, but is more specific
Psoriatic Arthritis
 Psoriatic arthritiscan have several presentations.
 The typical onset is as an oligoarticular arthritis that
may evolve into a symmetric small and large joint
polyarthritis resembling RA.
 The involvement of the DIP joints, presence of
psoriatic plaques, and the absence of rheumatoid
factor support the diagnosis.
Systemic Rheumatic Disease
 Systemic lupus erythematosus frequently presents as
a symmetric polyarthritis that may be confused with
RA if other extra-articular manifestations have not yet
 The arthritis may be migratory or inter-mittent and
extremely painful.
 Synovial proliferation is not as evident as with RA but
can lead to RA-like deformities. Notably, articular
erosions are not present on radiographs, even in
patients with a deforming arthritis.
Systemic Rheumatic Disease
 Drug-induced lupus presents with a symmetric
polyarthritis associated with systemic manifestations
such as fever and serositis.
 Other systemic rheumatic diseases can have an
inflammatory polyarthritis, including mixed
connective tissue disease and systemic sclerosis.
Patients with these diseases will also have Raynaud’s
disease and skin thickening.
 Patients with polymyositis and dermatomyositis may
have a polyarthritis accompanied by proximal muscle
weakness and/or a characteristic rash.
Other Systemic Illnesses
 Hepatitis Cviral infection may be associated with a chronic
polyarthritis resembling RA.
These patients may have a high titer rheumatoid factor but
negative anti-CCP antibodies and no erosions on radiographs.
Cryoblobulinemia, hypocomplementemia, and vasculitis may be
Any patient with polyarthritis and elevated liver-associated
enzymes should be evaluated for hepatitis C infection.
Multicentric reticulohistiocytosis can also cause a destructive
arthritis that mimics RA. Involvement of the DIP joints and the
presence of periungual nodules should help define the diagnosis.
 Osteoarthritisis the most common cause of an asymmetric non
inflammatory polyarthropathy as well as an asymmetric
oligoarticular arthritis with or without axial involvement.
Primary generalized “nodal” osteoarthritisis an asymmetric noninflammatory arthritis characterized by Bouchard’s nodes in the
PIP joints and Heberden’s nodes in the DIP joints of the hands.
Other joints characteristically involved are the first CMC,
cervical and lumbar spine, hips, knees, and first MTP joints.
Pain is aggravated by weight bearing and motion.
On examination, bony enlargement from osteophytes and
crepitus from roughening of articular cartilage may be detected.
Non-inflammatory synovial fluid may be detected as an effusion,
particularly in the knees.